Project 3 - Characterizing the Amplification Factories of Epstein-Barr Virus and Kaposi's Sarcoma-associated Herpesvirus

项目 3 - 描述 Epstein-Barr 病毒和卡波西肉瘤相关疱疹病毒的扩增工厂

• 批准号: 10910337
• 负责人: WILLIAM M. SUGDEN
• 金额: $ 11.46万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10910337
• 关键词: Antiviral Therapy; Architecture; Binding; Carcinoma; Cell Nucleus; Cells; Chromatin; Coupled; DNA; DNA Repair Gene; DNA biosynthesis; DNA-Directed DNA Polymerase; Equipment; Exclusion; Fluorescence Microscopy; Funding; Gene Expression Regulation; Genes; Genetic Transcription; Genome; Herpesviridae; Histones; Human; Human Genetics; Human Herpesvirus 4; Human Herpesvirus 8; Infection prevention; Late Gene Transcriptions; Learning; Life; Life Cycle Stages; Lymphoma; Lytic Phase; Malignant Neoplasms; Mediating; Microscopy; Molecular Biology; Molecular Chaperones; Molecular Genetics; Nuclear; Nuclear Envelope; Nucleocapsid; Oncogenic Viruses; Persons; Phase; Plasmids; Process; Productivity; Property; Proteins; Site; Source; Statistical Data Interpretation; Structural Protein; Structure; Transcript; Transmission Electron Microscopy; Viral; Viral Genes; Viral Proteins; Virus; Virus Replication; Visualization; Work; light microscopy; live cell imaging; new technology; recruit; sarcoma; transcription factor; transmission process; tumor; vaccine access; viral DNA

PROJECT 3 − SUMMARY/ABSTRACT Epstein-Barr Virus (EBV) and Kaposi's Sarcoma Herpesvirus (KSHV) cause lymphomas, carcinomas, and sarcomas in people across the world. No specific anti-viral therapies or vaccines are available now to treat these tumors or to prevent infections with EBV or KSHV. During the current funding period, we have developed new technologies and used them to uncover exciting discoveries about entry into and progression through the productive or lytic phase of the life-cycle of EBV. We have developed live-cell imaging of intact, infectious genomes of EBV and KSHV and found that during its lytic cycle EBV amplifies its DNA in discrete sites or factories, mediates a dramatic concentration of cellular chromatin at the nuclear periphery, and inhibits synthesis of histone chaperones. We have also found that this amplified viral DNA lacks histones and is the template for viral late gene transcription. We shall examine at the single cell level the formation of both EBV's and KSHV's amplification factories, their consolidation of cellular chromatin, and their mechanisms of transcription of viral late genes in these factories. These detailed studies will identify virus-specific processes that can be targeted to block virus spread.

项目3-概要/摘要 EB病毒（EBV）和卡波西肉瘤疱疹病毒（KSHV）引起淋巴瘤、癌和淋巴瘤。 肉瘤的发病率。目前尚无特异性抗病毒疗法或疫苗可用于治疗 这些肿瘤或预防感染EBV或KSHV。在目前的融资期内，我们 开发新技术并利用它们来发现有关进入和发展的令人兴奋的发现 通过EBV生命周期的生产或裂解阶段。我们已经开发了完整的活细胞成像， 感染性基因组的EBV和KSHV，并发现在其裂解周期EBV扩增其DNA离散 在核周围介导细胞染色质的显著浓度，并抑制 组蛋白伴侣的合成。我们还发现，这种扩增的病毒DNA缺乏组蛋白， 病毒晚期基因转录模板。我们将在单细胞水平上研究两种EBV的形成， 和KSHV的扩增工厂，它们对细胞染色质的整合，以及它们的作用机制， 病毒晚期基因的转录。这些详细的研究将确定病毒的具体过程 可以有针对性地阻止病毒传播。